This application proposes to establish an adult AIDS Clinical Trials Unit in Philadelphia, combining resources from two major medical centers, the University of Pennsylvania and Thomas Jefferson University. 140 patients/year will be enrolled in clinical trials, 80 at the Hospital of the University of Pennsylvania (HUP) and 60 at Thomas Jefferson University Hospital (TJUH). These include 60-75 with primary HIV infection (enrollment at both centers), 40-60 with opportunistic infections (enrollment at both centers), 10 with HIV related malignancies (enrollment at HUP primarily), and 10 with neurologic complications of HIV disease (enrollment at HUP primarily). The addiction treatment clinic at Girard Medical Center will serve as a site for enrolling HIV infected intravenous drug users (IVDUs). The TJUH group follows a large population of pregnant women who are IVDUs, approximately 15% of whom are HIV infected. The large Hemophiliac Center at TJUH will be a major source of patients for study. Approximately 50% of HIV positive patients treated at our two centers are minorities, and 15-20% are women. We also propose to establish Core laboratories in virology at Penn and pharmacology at Jefferson. The virology lab will perform all protocol mandated viral studies, and in addition quantitative cultures, quantitative PCR, assays to detect HTLV-I or -II infection in IVDUs, and assays to monitor HSV, CMV, and VZV isolates for emergence of resistance to antivirals. The pharmacology lab will provide analytical and pharmacokinetic support for protocols of investigational agents. A developmental virology project is proposed for TJUH that evaluates a new technique, in situ PCR, for detection of HIV-1 genome within intact cells. In addition, quantitative RNA PCR will be used to evaluate changes in HIV transcription that occur in response to therapy. This application brings together experienced investigators and offers a large community of HIV infected patients an opportunity to participate in NIH sponsored clinical trials.